ABSTRACT
Background: The patent literature contains a large amount of information on the internal state of current industrial technologies that are not available in other literature studies. Scientific articles are the direct achievements of theoretical research in this field and can reveal how current theories in basic research have developed. In this study, the progress and status of natural anticancer products in this field were summarized, and the research hotspots were explored through the analysis of the relevant patent literature and scientific articles. Methods: Patent data were retrieved from the incoPat patent retrieval database, and paper data were retrieved from the Web of Science core set and PubMed. GraphPad Prism 8, Microsoft Excel 2010, and CiteSpace 5.8.R3 were used to perform visual processing. The analyzed patent literature includes the patent applicant type, country (or region), and technical subject. The analyzed scientific article includes academic groups, subject areas, keyword clustering, and burst detection. Results: A total of 20,435 patent families and 38,746 articles were collected by 4 January 2022. At present, antitumor drugs derived from natural products mainly include 1) apoptosis inducers such as curcumin, gallic acid, resveratrol, Theranekron D6, and gaillardin; 2) topoisomerase inhibitors such as camptothecins, scaffold-hopped flavones, podophyllotoxin, oxocrebanine, and evodiamine derivatives; 3) telomerase inhibitors such as camptothecin and isoquinoline alkaloids of Chelidonium majus, amentoflavone, and emodin; 4) microtubule inhibitors such as kolaflavanone, tanshinone IIA analog, eugenol, and millepachine; 5) immunomodulators such as fucoidan, myricetin, bergapten, and atractylenolide I; 6) tumor microenvironment regulators such as beta-escin and icaritin; 7) multidrug resistance reversal agents such as berberine, quercetin, and dihydromyricetin; and 8) antiangiogenic and antimetastatic agents such as epigallocatechin-3-gallate, lupeol, ononin, and saikosaponin A. Conclusion: Anticancer natural product technology was introduced earlier, but the later development momentum was insufficient. In addition, scientific research activities are relatively closed, and technical exchanges need to be strengthened. Currently, the development of medicinal plants and the research on the anticancer mechanism of natural active products are still research hotspots, especially those related to immune checkpoints, essential oils, and metastatic cancer. Theories of traditional Chinese medicine (TCM), such as "restraining excessiveness to acquire harmony," "same treatment for different diseases," "Meridian induction theory," and "Fuzheng Quxie," have important guiding significance to the research of anticancer mechanisms and the development of new drugs and can provide new ideas for this process. Systematic Review Registration: [https://sourceforge.net/projects/citespace/], identifier [000755430500001].
ABSTRACT
Background: Adverse drug reactions with an outcome of death represent the most serious consequences and are inherently important for pharmacovigilance. The nature and characteristics of drug-related deaths are to a large extent unknown in the Chinese population. This study aims to characterize drug-related deaths by analysis of individual case safety reports (ICSRs) with an outcome of death in China. Methods: The characteristics of death ICSRs were analyzed by descriptive statistics of a large multi-provincial pharmacovigilance database in China. Results: There were 1,731 ICSRs with an outcome of death, representing 0.95% of all serious cases and 0.05% of all reported ICSRs. Most death ICSRs (78.57%) were reported by medical institutions. Only 16.00% of death ICSRs were reported by manufacturers or distributors. The reporting rate of death ICSRs in the age group of 0-4 years was significantly higher than patients aged 5-64 years. Patients aged over 64 years had the highest reporting rate of death ICSRs. Male patients generally had a higher reporting rate of death ICSRs than female patients. However, the reporting rate of female patients exceeded that of male patients in the age group of 20-34 years. Among 3,861 drugs implicated, ceftriaxone sodium with 146 (3.78%) records of death ranked first. Dexamethasone with 131 (3.39%) records of death ranked second. Qingkailing, an injectable traditional Chinese medicine with 75 (1.94%) records of death, ranked the fifth most frequently implicated medicine. Conclusion: Young children and elderly patients have a higher risk of drug-related deaths than patients aged 5-64 years. Female patients generally have a lower risk of drug-related deaths than male patients. However, female patients of reproductive age (aged 20-34 years) have a higher risk of drug-related deaths than male patients, hinting that physiological changes and drug uses for child bearing, giving birth, or birth control may significantly increase the risk of death for female patients aged 20-34 years. This paper suggests more research on the safe use of drugs for young children, elderly patients, and female patients of reproductive ages. Pharmacovigilance databases can be valuable resources for comprehensive understanding of drug-related problems.
ABSTRACT
WHAT IS KNOWN AND OBJECTIVE: Although superseded by other antiviral agents in many Western countries, vidarabine is still widely used in some countries, including China; hence, the extent and appropriateness of vidarabine prescriptions in children require better characterization. This study examined the rationale, extent, and health risks associated with irrational off-label vidarabine use in China. METHODS: Data used in the study were extracted from a multi-provincial joint adverse drug reactions monitoring platform from 2002 to 2018. Descriptive statistics were used to analyse the characteristics of individual case safety reports (ICSRs) related to vidarabine use. RESULTS AND DISCUSSION: Among 2772 individual ICSRs related to vidarabine, 2223 (80.19%) cases occurred in patients aged 0-9. In all patients, the median age and interquartile range were 2 (0-6). Although most adverse events were mild, five deaths were recorded, all in children below 7 years of age. Paediatric use is the most prominent off-label use of vidarabine. Additionally, several other irrational off-label uses were identified, including 218 (7.86%) cases of overdosing and numerous applications beyond the approved indications, dosages, routes of administration, and solvents. WHAT IS NEW AND CONCLUSION: Data indicate that vidarabine was mainly prescribed for suspected common viral infections in paediatric patients, demonstrating serious inappropriate off-label uses. The problem was further complicated by the lack of sufficient information regarding safety, efficacy, and dosing regimens in children, as well as by several additional risk factors such as inappropriate solvents, routes of administration, and overdose. In the case of children, the physicians' lack of understanding of antiviral activities and compassionate prescriptions were mainly responsible for drug overuse. The health risks associated with the paediatric use of vidarabine in China require greater attention and further investigation.
